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At two weeks old, Jo Wilson was left by her mother at a fire station. She was shuffled among numerous foster homes until age 16, when she began living independently out of her car. Her teacher, Ms. Schmitt, would let her into the school building early to do laundry. Jo worked furiously to get through school, graduating as high school valedictorian and moving on to Princeton University, graduating cum laude. Wilson attended Harvard Medical School, where she graduated at the top of her class. Wilson confessed to Alex Karev that Ms. Schmitt was the only person who supported her by saying, "[at graduation], I had one person: Ms. Schmitt."

Jo started her internship at Seattle Grace Mercy West Hospital shortly after the plane crash. She quickly learned, along with the other interns, to fear Meredith Grey, dubbing her Medusa. Meredith was put in charge of choosing an intern for the intern appy and she chose Jo. In surgery, Jo froze as expected when she ripped the cecum after removed the appendix and Meredith had to finish the surgery.

When she was found crying by Owen after the surgery, he told her not to stand in the hallway and cry, to cry somewhere else where he didn't have to see her. He explained to her that the intern appy is designed for her to fail and it sets her as the example. She then asked why Meredith was so mean. She knew that Meredith had been in a plane crash and wondered if that was why. Owen replied that Meredith isn't mean; she's strong. ("Going, Going, Gone")

When she wanted to scrub in on a surgery, she flirted with Callie to try to make it happen. However, Callie pointed out that Jo looked terrified that Callie might take her up on that offer, meaning she probably isn't into ladies. Callie told her not to trade sex for scrubbing in because that's skanky, to save it for actually getting to cut. Then she sent her to go suck up to Alex instead. He said no and when he saw her watching from the gallery, he sent her away. Later, when he scolded her for charting when she hadn't scheduled a consult for him, she began to cry, freaking him out. He invited her to scrub in on a surgery with him. ("Love the One You're With")

When given an opportunity to do something none of the other interns had done yet, Jo jumped at the chance. However, when she froze in the OR, she went to Arizona Robbins and told her what had happened, saying she believed Alex set her up to fail. Alex later came to her and told her that he was trying to let her to do something cool, but she freaked out. She said she was paranoid because her life has taught her that she can't trust anyone, but he informed her that she needs to get over it. ("Run, Baby, Run")

At Bailey's wedding, she had a drink, so when the doctors were called back to the hospital after a motorcycle crash, she was unable to go with them. Instead, she continued to drink with Alex. They got drunk and broke into a hotel room, where the raided a mini-bar. ("Things We Said Today")

When she heard about the plan to sell the hospital for parts, she admitted to Alex that she was sad and didn't want not to see him anymore, because she liked that he would talk to kids about pulling tiny little men out of their bellies. ("This is Why We Fight")

Jo and the other interns started referring to Jason as "Chest Peckwell." Alex took an immediate distaste to him, even going so far as to gang up with a patient and Dr. Webber to prank him, to which Jason responded with a snide comment about "nailing Jo in the bathroom." ("Idle Hands")

When she told Alex Karev that she was planning to move in with Jason, he was initially very angry with her. However, after working with Jason on a case, he told Jason that he was just protective of Jo because he had been in a similar situation to Jo as a child, though he never had it quite as bad as she did. He was unaware that Jo had not told Jason any of this. When Jo found out that Jason knew, she became angry with Alex for telling him. ("Sleeping Monster")

After a heated fight which involved Jason hitting Jo, she fled to Alex's house. He settled her into his bed. When Alex showed up at the hospital with Jason, who had been severely beaten, Meredith and Cristina assumed that Alex had done it, but it turned out that Jo herself had done it. When he grabbed her arm, she fought him off and he fell back and hit his head on the fireplace. She claimed he was fine when she left and still yelling. ("Readiness is All")

During the super storm, Jo helped to bag the babies in the NICU and then later to teach the parents how to bag their own babies. Arizona told Alex that Jo was great that day and if he's going to take credit for making his ladies crazy, he should take credit for helping make them great. Alex found Jo later and confessed his love. They shared a kiss. ("Perfect Storm")

After their first kiss, Alex and Jo went to an on-call room to make out. Alex wanted to wait to do it at his house, but Jo reminded him that there was a tree in his house and removed her scrub top. They continued kissing until Jo asked them if he had sex with Heather and Leah in that particular room. He confirmed, but Jo decided she could move past this and they continued kissing. He got paged, and she asked him to ignore his page. This made her think about dead people so they gave up. They went to the ER to help out treating the storm victims, which was impeded by the fact that they were all low on supplies and that the electric charts were still down. Meanwhile, she and the other interns also waited for news on Heather, who was being operated on. In a supply closet, Jo talked to Alex about her fear that Heather would die, only ending up to start kissing him again. However, it turned out Alex also had had sex with other interns in that closet, so Jo decided it wasn't going to happen there and left. ("Seal Our Fate")

After Heather's death, the mourning interns, who got the night off, decided they would all wait together for Heather's mother to arrive, as none of them wanted to do it on their own. They started looking for kind Heather stories to tell Maura and decided to look for Derek to hear about her talent for neurosurgery, but Meredith told them the mother wouldn't care about that and told them the story that she told George's mother back when he had died. Jo then met Alex in a lounge and told him that she and the others apparently weren't a tight group. They joked a little about the future of their relationship and he gave her a bottle of liquor that would help her and the others to come up with stories. Jo went to her fellow interns in the dressing room, where they started drinking. They realized that they knew nothing about each other, despite all the time they spent together. They decided to play circle of trust, during which Jo revealed to have been a street kid. Not long after, Maura Brooks arrived, and they stole Meredith's story. They then sat with her until Derek arrived to tell her what happened to Heather. Early in the morning, Derek met with the interns in the ER waiting room and thanked them for having stayed with Maura. He told them to go home, but Shane decided to ride out with the firefighters to the mudslide instead. Jo, Stephanie and Leah declared him crazy, but suddenly Stephanie stood up too and gave a speech that made it clear to Leah and Jo that they should stick together. Jo and Leah then got up too, and followed Stephanie and Shane to the ambulance bay to ride out to the mudslide with the firefighters. ("I Want You With Me")

After Heather's death, the interns began all sleeping at Alex's house and studying. Jo was waiting for Alex to proposition her so they could have sex and Alex was waiting because he thought she was still grieving, so he said they could stay there as long as they wanted. Jo went to the others and said that they needed to leave. That night, Jo went to Alex's house to wait for him. He came home and she said she was not an unfeeling person, but she wanted to have sex. He picked her up and carried her upstairs. ("Everybody's Crying Mercy")

At the fundraising gala, Jo spoke to donors on Alex's behalf, but pressured him to talk to them himself. When Alex left to go back to the hospital, Jo was upset. She went back to the hospital and found him drawing blood from himself. She believed he was doing drugs, but he corrected that he believed his father was in the hospital, so he was drawing blood to check. When the results came in, Alex decided he didn't want to know just before Jo told him that it was his father. ("Puttin' on the Ritz")

When the time came for Alex's father to be discharged, Jo got him set up for 28 days in a rehab facility. He declined and left the hospital. ("I Bet It Stung")

When Alex didn't come home for several nights, Jo was concerned that he was seeing someone else, but she figured out that it was about Alex's dad. ("Map of You")

Jimmy later returned in withdrawal. Jo treated him over Alex's objections. ("Man on the Moon")

After speaking to Jimmy and telling him that Jimmy leaving when he was a kid was better for all of them, Alex went to the wedding and told Jo that they were all they needed and that they'd be together forever. She agreed, but didn't realize that he meant it as a marriage proposal. ("Get Up, Stand Up")

When Jimmy's wife came to the hospital after Alex lied to her and said that Jimmy was dead, Alex introduced Jo as his fiancée, confusing her. She confronted him about it, saying she wasn't leaving him, but she wasn't ready for marriage. ("Take It Back")

Jo was upset to hear about the non-fraternization policy. She said that since they spend so much time at the hospital, they don't have time to meet anyone else. When she found out that one of the residents had filed the claim that led to the policy, she immediately assumed that Stephanie had filed it and was cold toward her. She later went to Stephanie when she found out that April and Jackson were still together. She said that Stephanie filing the claim was ruining her life, but Leah confessed that she filed the claim and explained why she did it.

Jo and Alex staged a fake fight and breakup so that people wouldn't think they were together. They started to sneak around the hospital, but after a rendezvous in a supply room, which Richard discovered, they were called into a meeting with the board. Alex came in and called them hypocrites before leaving. ("You've Got to Hide Your Love Away")

After Alex was suspended for violating the policy, Meredith began to look into options for them. She got them a love contract and said if they signed it, HR said it was okay if they continued to date. Alex was worried about Jo leaving him if he asked her to sign the contract. ("Throwing it All Away")

When Alex presented Jo with the contract, she told him she wouldn't sign it. Alex later assured her that the contract wasn't a commitment and that she wouldn't count on him, but said that he wanted to kiss her whenever he wants to kiss her and the contract would allow him to do that. ("We Gotta Get Out of This Place")

When a case came in of two sisters, one of who had developed three kinds of cancer in her lifetime, Richard told the residents to do research on Li-Fraumeni, as that's the condition the girl had. They did the research and developed a treatment plan, but Rory Williams had already died. ("You've Got to Hide Your Love Away")

At Richard's birthday party, Owen asked him to be director of the residency program because he noticed how well he'd been mentoring the residents. ("We Gotta Get Out of This Place")

Derek, warned that he wasn't teaching enough, took all the residents to work on a case with him that he had rescheduled several times. As the OR wasn't available until 1 AM, he then took them to the ER to work on the incoming patients, including having them work on a patient who was already dead so they could work with real brain tissue. When a man came in with scissors puncturing his forehead, they took him into an OR for a controlled extraction. Jo extracted the scissors after Leah was unable to pull hard enough. Then they went back to the case of Nova Jenkins. Each of the residents took a turn to step up to the microscope and ask a question so they could learn. ("Go It Alone")

While Jo was on scut, she was working on several cases at once. She found that she couldn't handle working on so many cases at once, at it put patients at risk. After a day of that, Jo overheard Owen and Richard talk about one of the residents not being cut out for surgery. Jo believed it was her. ("We Are Never Ever Getting Back Together")

When a patient with tetanus had a spasm that snapped his arm, Jo was concerned that she had broken the patient's bone. She worked on the case with Callie. While working on the case, she discovered that she has a knack for ortho. ("You Be Illin'")

Jo was used to test the emotion-reading machine Callie and Derek had gotten for their trial. She didn't have a positive response to the expected stimuli, but when Callie mentioned an ortho injury that came into the ER, Jo lit up. ("I'm Winning")

Jo continued to work with Callie on ortho cases and loved it. ("Change of Heart")

She worked with Callie on an ortho case after hearing that one of the residents was about to be fired. In an attempt not to get fired, she continued to suck up to the attendings. Callie noticed this and said that she needed to have grit if she planned to continue working in ortho. ("Everything I Try to Do, Nothing Seems to Turn Out Right")

Jo had a crush on Jason when she started working at Seatle Grace Mercy West Hospital. Jo and the other interns gave Jason the nickname of Chest Peckwell. Eventually, Jo and Jason began a romantic relationship. However, Jason and Alex constantly butted heads over allegations that Alex had feelings for Jo. Alex would inform Jason of Jo's troubled past, causing an argument. During that argument, Jason physically harmed Jo, causing her to move out and end the relationship. It was later revealed that Jo nearly killed Jason when she fought back, even to the extent of a brain bleed. He demanded to see the police, but was convinced otherwise after being threatened by Alex.

Shortly after first meeting her and telling her that he likes "chicks with boy names," Jo assured Alex that as he had already slept with all of her friends, she wasn't interested in him. ("Love the One You're With")

Alex Karev frequently referred to Jo Wilson as "princess" due to her so-called 'prissy' manners and attitude. She revealed to Alex her past life difficulties and the two became close friends after bonding at Bailey's wedding. They got along very well and they often drank together. However, they hit a snag when Jo began dating Jason Myers. After a huge fight between Jo and Jason, Jo revealed to Alex that Jason had hit her during the argument. Alex admitted to Cristina that he loved Jo, but that he was scared to tell her because of past failed realatonships. During the super storm, Alex finally admitted to Jo that he loved her and the couple shared a kiss. Since then, they have been dating. They hit a bit of a rocky patch when Alex's dad came into the hospital from a car crash related to drugs. Alex asked Jo to do a paternity test and he said he didn't want to know at the same time she said "he's your father." Alex then proceeded to stalk his father at bars where he was performing. When Alex didn't come home for 3 nights in a row, Jo got worried. He then told her what was happening and they worked it out.

When Alex's father returned to the hospital going through withdrawal, Jo tried to handle him, but found herself in over her head. Alex told her it wasn't her fault and that he'd been this way his whole life. At April's wedding, Alex told Jo that they would be together forever and were the only family each other needs. He said that if they do have kids, they will be great parents and will not need anyone else then share a passionate kiss. When Alex called Jo his fiancée, she told him that she didn't realize his speech at the wedding was a proposal and that she was not walking out on him, but she wasn't ready for marriage. She comforted Alex when his dad died.

When Leah issued a complaint to HR, the non-fratinization rule was put in place, forbidding unmarried couples of different authority levels to continue seeing each other. Alex and Jo faked a fight in front of the hospital, allowing them to believe they broke up while secretly staying together. Meredith gave Alex a love contract for them both to sign so they could continue working and seeing each other without getting into trouble. When Jo refused to sign it, Alex assured her that it wasn't a scary document to anything. She can't count on him because anything could happen at any minute. The contract just made it so that he could kiss her when he wants to. She signed and they shared a kiss. When Alex was offered a new job at a pediatric private practice, he sought Jo's advice and she was very supportive of him. She told him that working two jobs made him like a double agent which is very sexy. Alex took the job and Jo was very proud of him, telling him he'll do great.

Dr. Wilson was named by Meredith Grey as the most promising intern, and was thus awarded the first surgery of the rotation, which is in fact given to interns they think will fail. As expected, she did fail to complete the surgery and while crying about it, Dr. Owen Hunt informed her that it was an exercise meant to be a learning experience. The surgery is "designed" for the chosen intern to fail to set an example for the other interns.

When Richard Webber asked Meredith to choose one of the residents to assist with the surgery on him, Jo Wilson was selected.

When a patient in the E.R. broke his arm due to a tetanic contraction, Jo scrubbed in with Callie on his fracture repair. She discovered a love of ortho, and has since been scrubbing in with Callie often.